Oxygen Saturation Sub-analyses Errors in the Dominant Meta-analysis Used to Deimplement Albuterol as a Therapeutic Option for Bronchiolitis.

Abstract

Objective: Clinical experience and patient-level physiological studies indicate that albuterol transiently reduces oxygen saturation, irrespective of the underlying respiratory condition causing the wheezing. Three revisions of the Cochrane review, Bronchodilators for Bronchiolitis (Review), have found that albuterol temporarily increases oxygen saturation. Rarely, these findings were even statistically significant, but the direction of effect is consistently opposite from physiological studies. In this study, we attempted to resolve this apparent paradox.

Methods: The original trial publications included in multiple oxygen saturation sub-analyses in the 2006, 2010, and 2014 updates of the Cochrane review were assessed for appropriate study inclusion, correctness of calculations, and correct analysis with respect to direction of effect. The studies were also reviewed to assess whether the data was correctly transferred to the meta-analysis software. We repeated the meta-analyses calculations after correcting for suspected errors and plotted the results of the meta-analyses as originally reported and in their corrected form on an albatross plot.

Results: We found data miscalculations, errors of transposition of albuterol and placebo data, the inclusion of inpatient data in outpatient analyses, and questionable study inclusions in the 3 Cochrane review updates. After corrections were made, the direction of effect of albuterol switched negative, albeit nonsignificantly, a finding most consistent with clinical and physiological observations. In addition, the very wide heterogeneity between the original meta-analyses disappeared.

Conclusion: After multiple suspected data flaws were corrected our reanalyses of the reported data confirmed that decreased oxygen saturation can be expected following administration of albuterol to infants presenting with bronchiolitis syndrome, thereby resolving the apparent paradox in favor of clinical observation and research physiology.